1. Field of the Invention
This invention relates in general to methods and apparatus for infusing medications into a patient subcutaneously. In particular, the invention relates to an infusion pump that is adapted for use with prepackaged containers for delivering medications to patients from the container to the subcutaneous region of the patient via a catheter or needle, and to infusion needle array devices.
2. Brief Description of the Related Art
Infusion sets and pumps are used to deliver various types of solutions subcutaneously to patients. There are many medical conditions that require the administration of liquid medicaments transcutaneously (through the skin) and subcutaneously for prolonged periods. Diabetes, for example, may be controlled by daily, or more frequent, injections of insulin. The ability to administer numerous small dosages of insulin has been proven to be the best way to insure tight glucose control for a patient. The National Institute of Health (NIH) conducted a long-term study of people with diabetes known as the Diabetes Complications and Control Trial (DCCT) were it was determined that the proper management of diabetes requires 4 or more injections of insulin per day. However, current devices either are not convenient, painless enough, or easy to use by patients. Syringes and insulin pens all require the patients to inject themselves and do not provide a convenient or discreet mechanism to accomplish medication delivery.
Since transcutaneous injections are painful and troublesome, and since each injection represents a possibility for infection, injections are spaced at intervals as far apart as possible, resulting in peak and valley concentrations of the medicament in the bloodstream or at the site in the body requiring the medicament, the peak concentrations occurring shortly after the administration of the medicament and the low, or valley, concentrations occurring shortly before the administration of the next injection. This method of administration exposes the patient to the possibility of overdose at peak levels and underdose at valley levels, but was nevertheless the standard method for many years in the absence of a better alternative.
Recently, systems have been developed in which a catheter is semi-permanently implanted in a patient to provide access to a transcutaneous site in a patient""s body, and a liquid medicament is supplied to the catheter from a reservoir. However, many patients find that the infusion site forms small red marks that are the result of irritation from the infusion at a single point. Infusing the medication either by bolus injection or reducing the amount of medication infused at any one specific site relieves this irritation.
Insigler and Kirtz (Diabetics, 28: 196-203, 1979) describe a portable insulin dosage regulating apparatus which uses an electrically driven mini-pump with an insulin reservoir to periodically dispense a predetermined number of insulin units (U). A small electronic control box is used to set the basal rate of 0.4 U/hr in stages of 0.2 U each. A switch is used to trigger a program that infuses a higher dose for a period of one hour, after which the system automatically goes back to the basal rate.
Thomas et al. U.S. Pat. No. 3,963,380, issued Jun. 15, 1976, describes a micropump driven by piezoelectric disk benders. Although the pump draws only a small current, it requires a voltage of about 100 volts to drive the pump.
Tamborlane et al. (The New England Journal of Medicine, 300: 573-578, No. 11, Mar. 15, 1979) describe a portable subcutaneous insulin delivery system which uses a battery driven syringe pump. The apparatus is bulky and heavy.
A peristaltic motor driven pump has been described by Albisser et al. (Med. Progr. Technol. 5: 187-193 [1978]). The pump weighs 525 g. and consumes 60 milliwatts at maximum pumping rates. This system has a continuous duty cycle. It is bulky and heavy and consumes a relatively large amount of power.
Additionally, a number of devices have been developed for administering insulin, drugs, or other substances to persons and animals. As self-administration of certain substances, such as insulin, is common, it is important that devices designed for self-administration be simple to operate, reliable, and accurate. The current devices available for the patient include syringes, pumps, or injection pens. Each of these devices do not provide for both a convenient, easy to use, and discreet means of injecting medication. The patients must inject themselves either in public, or use expensive bulky devices.
The different types of infusion pumps in the prior art include elastomeric pumps which squeeze the solution from flexible containers, such as balloons, into tubing for delivery to the patient. Spring loaded pumps have also been provided to pressurize the solution containers or reservoirs. Infusion pumps have also been provided with cartridges containing flexible compartments that are squeezed by pressure rollers for discharging the solutions, such as the pump shown in U.S. Pat. No. 4,741,736. These types of infusion pumps, however, require special containers and are not adaptable for using standard pre-filled single dose containers for solutions.
Where infusion pumps cannot use the standard pre-filled single dose containers, it is necessary to separately fill the containers with the medication from larger vials. The transfer of medication to the cartridges, balloons, reservoirs and other specialized containers is a difficult and problematic process for people with chronic illnesses such as diabetes who must take insulin to adequately process their glucose. The need has therefore been recognized for an infusion pump system which obviates the limitations and disadvantages of existing pumps of this type, and which is adapted for use with standard pre-filled single dose containers
Additionally, the currently available devices for infusing medication subcutaneously require the patient to insert a needle or flexible catheter through the skin into the subcutaneous region. Patients find this either painful, inconvenient, or very invasive. The result is that the majority of patients do not utilize pumps and infusion sets which have a major advantage over traditional injection therapy consisting of periodic injections with syringes.
Morphologically, the composite epithelial layer of the skin, also called the epidermis, is the part of the skin endowed with the barrier against penetration, and it consists of four layers. These layers are an outermost layer called the stratum corneum and three underlying layers, called the stratum granulosum, the stratum malpighii, and the stratum germinativum. The stratum corneum is a heterogenous layer of flattened, relatively dry, keratinised cells with a dense underlying layer commonly called the horny layer. In the past, it was generally held that this horny layer acted as the barrier to the penetration of external substances into the body. See J. Invest. Dermat., Vol 50, pages 19 to 26, 1968. Now, it is generally held that the whole stratum corneum and not a discrete cellular layer functions as a barrier to the penetration of substances into the body. The whole stratum corneum is considered to be a barrier because of a chemical keratin-phospholipid complex that exists in the stratum corneum and acts along with the horny layer as a barrier to the penetration of substances into the body. For the purposes of the present invention, the whole stratum corneum is considered as the natural barrier to penetration. J. Invest. Dermat., Vol 50, pages 371 to 379, 1968; and, ibid, Vol 56, pages 72 to 78, 1971.
The stratum corneum, which is about 15 microns thick when dry and about 48 microns thick when filly hydrated, acts as a barrier for an extremely large variety of compounds. The barrier is maintained for compounds with large molecular volumes, for compounds substituted with functional groups, for small soluble molecules, for non-electrolytes, and the like. See J. Invest. Dermat., Vol 52, pages 63 to 70, 1969. Once a compound is made to pass through the stratum corneum, for example, by surgically stripping the stratum corneum, there is no major hindrance to penetration of the remaining epidermal layers or the dermis. After this, the compound enters into the circulation via the capillaries. See Progress in the Biological Sciences in Relation to Dermatology, 2nd Ed., pages 245, 1964, Univ. Press, Cambridge; and, J. of Drug and Cosmetic Ind., Vol 108, No. 2, pages 36 to 39 and 152 to 154, 1971.
In view of the above presentation, once a drug has penetrated through the stratum corneum, for example with the aid of the drug delivery device of the present invention, penetration through the remaining layers of the skin proceeds readily. However, drugs such as insulin must be delivered into the dermal area, that is, between the superficial vascular plexus and the deep vascular plexus, to insure uniform and consistent absorption by the body. Absorption of a drug into the stratum corneum with no further penetration is considered retention and not percutaneous penetration.
Other prior devices and methods include U.S. Pat. No. 3,964,484, U.S. Pat. No. 4,235,234, U.S. Pat. No. 4,969,871, U.S. Pat. No. 6,083,196, U.S. Pat. No. 6,050,988, U.S. Pat. No. 5,587,326, U.S. Pat. No. 6,022,316, U.S. Pat. No. 4,883,472, U.S. Pat. No. 4,865,591, U.S. Pat. No. 4,973,318, U.S. Pat. No. 5,017,190, U.S. Pat. No. 5,279,586, U.S. Pat. No. 4,856,340, U.S. Pat. No. 4,313,439, U.S. Pat. No. 5,640,995, and U.S. Pat. No. 5,327,033, the contents of each of the which is incorporated herein by reference in their entirety.
Various micro actuators have been developed to drive a variety of mechanisms including pumps and linear motion devices. The development of these devices does not provide a small enough or low cost discrete solution to medication delivery. From a review of the current art for expelling medication from a prefilled cartridge it is clear that the devices are of substantial size and bulky.
U.S. Pat. No. 5,644,177 discloses micromechanical structures capable of actuation for purposes such as fluid flow control which are formed on substrates in sizes in the range of one or two millimeters or less using micromechanical processing techniques. A magnetic core having a gap therein is fixed on the substrate, and a plunger is mounted by a spring for movement parallel to the substrate in response to the flux provided to the gap of the fixed core. An electrical coil wound around a mandrel is engaged to the fixed magnetic core such that flux is induced in the core when current is supplied to the coil, driving the plunger against the force of the spring. A micromechanical fluid control unit includes a metal frame structure formed by electrodeposition on a substrate with the inner wall of the frame having slots formed therein to admit a separator wall which divides the interior of the frame into separate chambers, with a cover secured over the top of the frame and the separator wall to seal the chambers. A plunger actuator can be mounted within the frame with fixed core sections extending through the walls of the frame, and with the mandrel and coil engaged to the fixed core sections outside of the frame to provide magnetic flux to a gap to actuate the plunger within the sealed enclosure.
U.S. Pat. No 5,914,507 discloses a micromechanical device or microactuator based upon the piezoelectric, pyroelectric, and electrostrictive properties of ferroelectric thin film ceramic materials such as PZT. The microdevice has a device substrate and a deflectable component. The deflectable component is mounted for deflection on the device substrate and has a sensor/actuator. The sensor/actuator has first and second electrodes and a piezoelectric thin film disposed between the first and second electrodes. The thin film is preferably PZT. The sensor/actuator is disposed on a sensor/actuator substrate. The sensor/actuator substrate is formed of a material selected for being resistive to attack by hydrofluoric acid vapor.
According to a first aspect of the invention, a system useful for dispensing medication comprises a foundation, a gripper including a first portion and a second portion spaced from the first portion, the first portion being movable toward and away from the second portion along a gripper direction, a first actuator which changes length in response to a stimulus, the first actuator partially secured to the foundation and positioned adjacent to the gripper first portion, the first actuator oriented relative to the gripper direction and positioned relative to the gripper first portion so that when the first actuator changes length in response to a stimulus the first actuator moves the gripper first portion along the gripper direction, a second actuator which changes length in response to a stimulus, the second actuator partially secured to the foundation and positioned adjacent to one of the gripper portions, the second actuator oriented relative to the gripper direction and positioned relative to said one of the gripper portions so that when the second actuator changes length in response to a stimulus the second actuator moves said one of the gripper portions along a direction different from the gripper direction.
According to a second aspect of the invention, a system useful for dispensing medication comprises a medication cartridge including a hollow barrel, and open end, and an outlet opposite the open end, a plunger slidably positioned in the barrel, a slide positioned in the barrel adjacent to the plunger and movable in the barrel along a slide direction, a first actuator which changes length in response to a stimulus, the first actuator partially secured to the slide, the first actuator oriented relative to the slide direction and so that when the first actuator changes length in response to a stimulus the first actuator moves the slide along the slide direction, and a second actuator which changes length in response to a stimulus, the second actuator partially secured to the slide, the second actuator oriented relative to the slide direction so that when the second actuator changes length in response to a stimulus the second actuator engages the barrel inside surface and holds the slide in the barrel.
According to a third aspect of the invention, a system useful for dispensing medication comprises a U-shaped flexible shaft, a solenoid movable between first and second positions, a pawl connected to the solenoid, a pinion having teeth and positioned with the pawl between the pinion teeth, a belt on the pinion, an arm attached to the belt and to the flexible shaft, wherein movement of the solenoid between the first and second positions moves the pawl, the pawl rotating the pinion, the pinion moving the belt, the belt moving the arm, the arm moving the flexible shaft.
According to a fourth aspect of the invention, a device useful for dispensing a liquid comprises a plurality of needles, the needles each including a sharpened end and being bent adjacent to the sharpened end, a base including bores in which the needles are at least partially inserted, the base including an annular space to which the bores extend, and a cap sealingly mounted to the base and forming a plenum space with the base, the plenum space including a portion of the base annular space, the cap including a fluid passageway in fluid communication with the plenum space.
It is a general object of the invention to provide a new and improved infusion pump which is adapted for use with pre-filled single dose containers and configured for use with a catheter or integrated skin interface device configured from a plurality of micro projections attached directly to the pump.
Another object of the invention is to provide a pump with an integrated skin interface device that breaches the stratum corneum with multiple hollow projections that penetrate the skin to the a depth that goes beyond the superficial vascular plexus but not as deep as the deep vascular plexus and is connected to a micro infusion device that is capable of providing a relatively constant infusion of medication or bolus injections on demand. This also provides a less painful infusion because the depth control of infusion devices of this invention do not penetrate as deep and disrupts the pain sensors in the skin. This also provides the patient a more comfortable infusion and minimizes the irritation from the infusion process
Another object of the invention is the formation of the small and compact infusion or injection system that is capable of being used separately to infuse or inject medication when attached to a catheter.
Another object is to provide an infusion pump which eliminates the need for the patients to separately transfer the medications into containers used with the pump, and thereby minimize costly and difficult preparation steps.
Another object is provide an infusion pump which accurately dispenses the medication at a controlled pressure and for a controlled period of time which enables the use of a micro projection skin interface device.
Another object is to provide an infusion pump which can include a mechanical drive system that is safe, low cost, and compact in size.
Another object is to provide an infusion pump which can achieve health benefits by lowering or obviating the risk of contaminating the medication by transferring the medication from a primary container to one which is compatible with the pump and providing an alarm in the case where the solution is not completely delivered to the patient.
Another object is to provide an infusion pump that is small in size to permit discrete infusion of medication.
Another object is to provide an infusion pump which accurately dispenses medication at a controlled pressure and for a controlled period of time.
Another object is to provide an infusion pump which includes a control system with is capable of supporting both basal rate delivery and bolus delivery.
Still other objects, features, and attendant advantages of the present invention will become apparent to those skilled in the art from a reading of the following detailed description of embodiments constructed in accordance therewith, taken in conjunction with the accompanying drawings.